The world faces an epidemic of atrial fibrillation and atrial fibrillation-related stroke. An individual's risk of atrial fibrillation-related stroke can be estimated with the CHADS(2) or CHA(2)DS(2)VASc scores, and reduced by two-thirds with effective anticoagulation. Vitamin K antagonists, such as warfarin, are underused and often poorly managed. The direct thrombin inhibitor dabigatran etexilate and factor Xa inhibitors rivaroxaban and apixaban are new oral anticoagulants that are at least as efficacious and safe as warfarin. Their advantages are predictable anticoagulant effects, low propensity for drug interactions, and lower rates of intracranial haemorrhage than with warfarin. A disadvantage is the continuing need to develop and validate rapidly effective antidotes for major bleeding and standardised tests that accurately measure plasma concentrations and anticoagulant effects, together with the disadvantage of possible higher rates of gastrointestinal haemorrhage and greater expense than with warfarin. The new oral anticoagulants should increase the number of patients with atrial fibrillation at risk of stroke who are optimally anticoagulated, and reduce the burden of atrial fibrillation-related stroke.